Shinji Ohara
Acute disseminated encephalomyelitis (ADEM) and Multiple sclerosis (MS) are both immunologically mediated inflammatory demyelinating disease of the CNS. ADEM and MS have long been considered as a separate disease entities, but clinical differentiation of ADEM from the first attack of MS is often difficult because of overlapping clinical features. Pathologically, perivenous demyelination and discrete confluent demyelination (plaque) have been generally regarded as the hallmark of ADEM and MS, respectively. It is also known that in contrast to MS, which shows quite diverse heterogeneous pathologic patterns, ADEM shows generally homogenous pathological features of inflammatory demyelination. However, hybrid cases showing pathological features of both ADEM and MS do exist, suggesting that ADEM may share some common underlying pathologic mechanisms with certain stages or subgroups of MS.
DOI: 10.29245/2572.942X/2017/6.1131 View / Download PdfShun Aritake, Hiroaki Oguro*, Kenichi Iwasa, Shingo Mitaki, Hiroyuki Takayoshi, Satoshi Abe, Keiichi Onoda, Shuhei Yamaguchi
We studied prognosis in 156 acute stoke patients treated by ozagrel and edaravone with the Japanese Standard Stroke Registry database in our hospital. They were examined as to their stroke types, neurological severity according to the NIH Stroke Scale (NIHSS) and clinical outcomes at admission by the modified Rankin Scale (mRS). Acute noncardioembolic stroke patients with lacunar and atherothrombosis showed functional recovery by both of ozagrel monotherapy and the combination therapy of ozagrel and edaravone. Although ozagrel monotherapy in atherothrombotic infarction showed most improved by 2.4 points, we did not find significant difference among four groups according to ozagrel monotherapy or the combination therapy in atherothrombotic or lacunar infarct after adjusted for age.
DOI: 10.29245/2572.942X/2017/6.1137 View / Download PdfNorishi Ueda
We previously reviewed clinical characteristics of all reported pediatric cases of Mycoplasma pneumonia (M.pneumoniae)-associated mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). It dominantly occurs in Asian and Caucasian children, suggesting age/race as predisposing factors of MERS. Fever is the most common non-neurological symptom, while more than half of the cases have no respiratory symptoms. Thus, M.pneuminiae-associated MERS may be underestimated and should be a differential diagnosis of febrile children with neurological abnormalities. The mechanism of the disease is unknown. However, susceptibility of immature corpus callosum in young children to immune response-mediated neuroinflammattory stimuli induced by M.pneuminiae, including interleukin-6, reactive oxygen species and toll-like receptors, rather than direct invasion of the organism in central nervous system may contribute to the pathogenesis of MERS. A role of autoantibodies awaits further investigations. Despite excellent prognosis in type I MERS, it remains elusive whether type II MERS is highly associated with neurological sequel.
DOI: 10.29245/2572.942X/2017/6.1133 View / Download PdfChiara Stella Di Stadio1, Filomena Altieri1, Giuseppina Minopoli1, Giuseppina Miselli1, Emilia Rippa1*, Paolo Arcari1,2*
Gastrokine 1 (GKN1) is a 18 kDa stomach protein highly expressed in normal gastric tissue but absent in gastric cancer. GKN1 plays its major role in maintaining gastric mucosal integrity. Because of the presence in its central region of a BRICHOS domain, GKN1 is characterized by multifunctional properties since it interacts and regulates the activity of several proteins. The BRICHOS domain consists of about 100 amino acids and has been found in protein families often associated with major human diseases like familial British and Danish dementia (BRI2) or respiratory distress syndrome (surfactant protein C) (SP-C), both associated with amyloid formation. It has been shown that BRICHOS is a chaperon domain that has the property of binding precursor protein regions with high β-sheet tendencies, thereby preventing them from amyloid formation. Like the BRICHOS domains from BRI2 and SP-C precursor (proSP-C), also GKN1 is able to prevent fibrils formation of amyloid-beta peptide (Aβ) and to interact with the C-terminal region of APP thus hindering the γ-secretase proteolytic sites. Indeed, amyloid is of great medical importance since it originates in several major fatal diseases such as Alzheimer, Parkinson and diabetes mellitus. The results collected until now on the BRICHOS properties of GKN1 and those from other BRICHOS suggest that the different amyloids recognized by BRICHOS should contain similar structural elements therefore, the BRICHOS domain represents a potential powerfull tool for therapeutic approaches against amyloid associated diseases.
Abbreviations: AD, Alzheimer disease; Aβ, amyloid-beta peptide; APP, amyloid precursor protein; CTFs, APP C-Terminal Fragments; GC, gastric cancer; DAPT, N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester; DMSO, dimethyl sulfoxyde; GC, gastric cancer; GKN1, gastrokine 1; flGKN1, full-lenght GKN1; MS, mass spectrometry; rGKN1, recombinant GKN1; SPR, surface plasma resonance; TM, transmembrane; TMpred, transmembrane prediction.
DOI: 10.29245/2572.942X/2017/6.1132 View / Download PdfChiara Cupidi, Valentina Laganà, Nicoletta Smirne, Amalia Cecilia Bruni*
Yoon-Sang Oh, Dong-Woo Ryu, Jee-Eun Lee, Joong-Seok Kim*
Cognitive dysfunction and dementia are important causes of disability and mortality in the elderly population. Over a decade, many studies have found evidence that greater arterial stiffness is associated with impaired cognitive function. Stiff arteries have a direct effect on the brain microvasculature. In this review, we present evidence that arterial stiffness is linked to cognitive dysfunction in neurodegenerative disorders represented by Alzheimer’s disease and Parkinson’s disease. We also discuss possible mechanisms of arterial stiffness and cognitive dysfunction other than the universal pathologic features of beta-amyloid for Alzheimer’s disease and alpha-synuclein for Parkinson’s disease.
DOI: 10.29245/2572.942X/2017/5.1130 View / Download PdfDOI: 10.29245/2572.942X/2017/5.1125 View / Download PdfSoon Young Park, Veerakumar Balasubramaniyan, and John F. de Groot*
Tarek Nafee, Dima Nimri, Gerald Chi, Serge Korjian, Yazan Daaboul, Douglas Arbetter, Megan Yee, Purva Jain, Seyedmahdi Pahlavani, Haleigh Williams, Nathan Michalak, Megan Merlo, Usama Talib, C. Michael Gibson*
Stroke is one of the leading causes of mortality and morbidity worldwide. It results in considerable costs to the healthcare system in the United States. Pharmacologic stroke prophylaxis has been well-studied in patients with atrial fibrillation and in patients with a history of stroke. In-hospital strokes constitute 2.2% to 17% of all strokes and often go undiagnosed in acute medically ill patients. A retrospective analysis of the APEX trial identifies an acutely ill hospitalized patient population that may benefit from extended duration prophylaxis. The hospitalized medically ill are a novel population to target for stroke prophylaxis. This article will discuss the primary results of the APEX sub-study and other trials that have demonstrated stroke reduction with extended duration anticoagulation in this population. This article additionally comments on the clinical relevance of these findings and the importance of the development of short-term risk stratification models to aid clinicians in deciding whether or not to provide pharmacologic stroke prophylaxis to their acutely ill patients at hospital admission.
Julien Leblond1, Anne-Claude Juillerat Van der Linden1,2, and Martial Van der Linden1,3*
The dominant biomedical position considers Alzheimer’s disease (AD) to be intrinsically different from normal ageing and other neurodegenerative diseases and proposes that, by pursuing extensive research on what are considered the specific neuropathological characteristics of AD (i.e., neurotic plaques and neurofibrillary tangles), we will eventually be able to identify the cause of this disease and develop medical treatments that will allow us to successfully cure it. However, results of numerous recent studies go against this essentialist and category-based view and instead suggest that the cognitive, emotional, behavioural, and functional difficulties that some people experience as they grow older are modulated by a myriad of factors and mechanisms that interact throughout the lifespan. Importantly, this alternative way of conceptualising Alzheimer’s disease implies a shift of focus in terms of research objectives and calls for significant changes in terms of neuropsychological assessment and intervention in clinical practice.
DOI: 10.29245/2572.942X/2017/4.1121 View / Download PdfValéria Meszlényi1, Roland Patai2, Bernát Nógrádi1, József I. Engelhardt3, László Siklós2
Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disorder characterized by the progressive loss of motor neurons in the central nervous system and neuromuscular junctions in the periphery. The pathomechanism behind the disease, except from some familiar cases associated with genetic mutations, remains unclear, however, numerous mechanisms contributing to the disease have already been disclosed. The key components are the oxidative stress, excitotoxicity, mitochondrial dysfunctions and inflammatory processes. In addition, increased intracellular calcium, which is another identified pathological event, could merge these individual toxic mechanisms into a single, escalating and self-perpetuating cycle of neuronal degeneration. Our previous results suggest that calcium homeostasis might be preserved by modulating the transmembrane calcium flux with therapeutic compounds or via altering the calcium binding protein content to maintain an enhanced calcium buffer capacity. The scope of this commentary is to accentuate the reciprocal calcium dependence of the pathological events associated with amyotrophic lateral sclerosis and to discuss possible therapeutic strategies based on the restoration of calcium homeostasis.
DOI: 10.29245/2572.942X/2017/4.1123 View / Download PdfDOI: 10.29245/2572.942X/2017/4.1126 View / Download PdfMagalie Chéron1 and Henriette Löffler-Stastka1*
Clare C. Yu1, Babu J. N. Reddy2, Juliana C. Wortman1, Steven P. Gross1,2
Long-distance intracellular axonal transport is predominantly microtubulebased, and its impairment is linked to neurodegeneration. Here we review recent theoretical and experimental evidence that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Theoretical work suggests that this opposition to motion increases rapidly as the cargo approaches the wall. However, having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus decreases the effects due to such opposition. Experimental evidence supports this hypothesis: in small caliber axons, microtubule density is higher, increasing the probability of having parallel microtubules close enough that they can be used simultaneously by motors on a cargo. For transport toward the minus-end of microtubules, e.g., toward the cell body in an axon, a recently discovered forceadaptation system can also contribute to overcoming such opposition to motion.
DOI: 10.29245/2572.942X/2017/3.1118 View / Download PdfA Duruflé1, C Le Meur1, P Gallien1, C Lozach1, MP Reillon1, N Clerc1, M Jambou1, B Nicolas1
Many mobile teams were created over the past decade in various medical specialties including physical medicine and rehabilitation.
The Pole Saint Helier has created a mobile team of reintegration - rehabilitation (EM2R) in December 2012 with support from the Regional Health Agency of Brittany. It operates on the health territory No. 5 of Brittany near people experiencing neurological disability. Its main mission is to implement the necessary devices to facilitate the home return of people hospitalized after a neurological event or maintaining to home people with neurological disorders.
The number of supported annual is about 200. People with brain lesions account for 2/3 of the population, mean age 60 years, with a high degree of dependence. The complexity of the patients become clearer with a minimum of two professionals involved by patient. Occupational therapy represents the majority of requests for intervention. New activities have emerged: supported to people with brain tumor, collaborations with palliative mobile teams and home hospital, formation and education of caregivers.
This activity outside is an alternative to the PMR care offer in link especially with the recommendations of the French Society of Physical Medicine and Rehabilitation and High Autority of Health on the organization of care pathway of stroke.
DOI: 10.29245/2572.942X/2017/3.1097 View / Download PdfKosmas Macha, Bastian Volbers, Bernd Kallmünzer
Direct Oral Anticoagulants (DOAC) are highly effective for the prevention of systemic embolism and ischemic stroke in non-valvular atrial fibrillation, but the optimal time point of treatment initiation after stroke has not been defined yet. The very early period after stroke bears a particular high risk of stroke recurrence and the timely initiation of secondary prevention at that early stage could therefore be most beneficial for the patient. Contrarily the use of DOAC in the hyperacute phase of stroke might increase the risk of bleeding complications. The prospective trials investigating the use of DOAC versus vitamin K antagonists did not include patients during the first weeks after stroke due to safety concerns. However, preliminary results from smaller cohorts suggest that the use of DOACs in this early time frame is feasible and safe. Larger prospective trials are warranted to confirm these results and investigate the efficacy of early treatment initiation.
DOI: 10.29245/2572.942X/2017/3.1112 View / Download PdfRicardo Vieira Botelho1, Juliete Melo Diniz1
Background: Adult craniocervical junction malformations have been described as Chiari malformation (CM) and Basilar invagination (BI). Recently, angular craniometric studies have identified differences among subtypes of malformations and reveled new relationships between skull and spine.
Objective: The scope of this study is to summarize the knowledge related to craniometric relationship in pathophysiology of these diseases.
Results: In CM, angular craniometric measures are not different from normal controls. In BI type I and II there is an increased craniocervical Kyphosis associated to cervical spine lordosis. Chamberlain’s line violation evaluation reveals that there is a downward angulation of the skull towards the upper cervical spine in BI.
Conclusion: BI should be considered a craniometrical kyphosis rather than a prolapse of the cervical spine to the skull base.
DOI: 10.29245/2572.942X/2017/3.1110 View / Download PdfAi-Ling Li1,2,3*, Yuan Bo Peng1
1Department of Psychology, The University of Texas at Arlington, 501 South Nedderman Drive, Arlington, Texas 76019, USA
2Department of Psychological & Brain Sciences, Indiana University Bloomington, 1101 E. 10th St., Bloomington, IN 47405, USA.
3Gill Center for Biomolecular Science, Indianan University Bloomington, 702 N. Walnut Grove Ave., Bloomington, IN 47405, USA.
Pain and depression are two major health issues that we are currently facing. Chronic pain is the main reason that people seek medical care; and numerous people commit suicide each year because of depression. These two pathological conditions often coexist. Chronic pain patients are more likely to develop major depressive symptoms, while depressed patients reported more pain symptoms than normal healthy population. Understanding the common mechanisms associated with depression and pain is important for developing the effective strategy to treat this comorbidity. In this review, the potential mechanisms that contribute to both depression and pain are discussed from four perspectives, the morphological changes in the brain, monoamine deficiency, brain-derived neurotrophic factor (BDNF) reduction in the hippocampus, and the hypothalamic-pituitary-adrenocortical (HPA) axis dysfunction.
DOI: 10.29245/2572.942X/2017/3.1116 View / Download PdfDOI: 10.29245/2572.942X/2017/2.1096 View / Download PdfTommaso Vannocci1, Annalisa Pastore1,2
1Maurice Wohl Institute, King’s College London, 5 Cutcombe Rd., London SE5 9RT, UK
2Molecular Medicine Department, University of Pavia, Pavia, Italy
Kolja Schürmann and Arno Reich
In-hospital stroke (IHS), which represents between 2.2% and 17% of all strokes, differs from community-onset stroke (COS) in etiology, treatment approaches and outcome. Patients hospitalized for cardiac disease are especially vulnerable to predominantly cardioembolic IHS. Stroke severity, functional outcome and mortality compare unfavorably to COS. Difficulties in symptom recognition, intra-hospital delays, various stroke mimics, critical underlying diseases and contraindications against standard systemic thrombolysis represent difficulties in IHS treatment. Quality of care may be improved by educating medical staff, implementing a code stroke and a CT-rendezvous system, providing access to specialized care (e.g. on stroke units) and endovascular reperfusion therapy as well as neuromonitoring, where applicable.
DOI: 10.29245/2572.942X/2017/2.1114 View / Download PdfBruno Fattori1, Gabriele Siciliano2, Amelia Santoro1, Salvatore Osvaldo Romeo1, Andrea Nacci1
Our purpose was to assess the relationship between the disease severity of Amyotrophic Lateral Sclerosis (ALS) and the main parameters of Fiberoptic Endoscopic Evaluation of Swallowing (FEES), indirectly hypothesizing for FEES a role as clinical indicator of the progression of ALS. We studied 220 patients (101 women, 119 men) with ALS; of these, 148 had spinal and 72 bulbar onset. They were analyzed according to the Amyotrophic Lateral Sclerosis Functioning Rating Scale (ALSFRS) and the b-ALSFRS subscale (bulbar scale). All subjects underwent FEES. Post-swallowing residue was classified into four classes (0-3); premature spillage and aspiration were considered either present or absent. An in-depth statistical analysis revealed a highly significant relationship between the FEES parameters studied and the severity of the disease assessed through ALSFRS and b-ALSFRS (p < 0.0001), no matter what bolus texture was used. Moreover, statistical analysis showed a highly significant association between the classes of severity in bulbar forms and all the FEES parameters, no matter what type of bolus was administered (p <0.0001), whereas a significant correlation in spinal forms only for post-swallowing residue with solid (p= 0.025) and semisolid (p= 0.034) boluses. FEES is a good indicator of the severity of dysphagia and of its progression in patients with ALS, as well as of the clinical progression of the disease.
DOI: 10.29245/2572.942X/2017/2.1113 View / Download PdfSean P. Didion, PhD1
Nitric oxide derived from endothelial nitric oxide synthase (eNOS) has been shown to be a major mediator of endothelium-dependent responses in cerebral blood vessels. Loss of a single eNOS gene is not associated with any apparent negative consequences on endothelial function in most blood vessels. In contrast, we have recently demonstrated that heterozygous eNOS gene deficiency in combination with a high fat diet is associated with marked impairment of endothelial function. These findings provide an important example of eNOS haploinsufficiency and one that directly impacts the cerebral vasculature. A major mechanism associated with the impairment of endothelial function with eNOS deficiency and a high fat diet appears to be related to increases in plasma IL-6 that serves to further reduce the bioavailability of NO either directly or indirectly via reductions in eNOS expression or activity and via increases in vascular superoxide. Taken together, these findings provide important insights into genetic and molecular mechanisms that promote endothelial dysfunction in response to a high fat diet in cerebral blood vessels with inherent reductions in eNOS gene expression, such as those due to eNOS gene polymorphisms. These findings also highlight the importance of eNOS+/- mice to study the effects of eNOS haploinsufficiency on cerebral blood vessels.
DOI: 10.29245/2572.942X/2017/2.1111 View / Download PdfDeepika Rajesh, H. Ian Robins* and Steven. P. Howard
The prognosis for patients with high-grade glioma remains dismal illustrating the need for the development of chemotherapeutic strategies intended to synergize with treatment modalities of proven efficacy such as radiation therapy. Karenitecin, (BNP1350,7-[(2-trimethylsilyl)ethyl]-20(S)-camptothecin), is a semisynthetic, orally administrable camptothecin, with physiochemical properties favoring increased accumulation of active drug within the central nervous system. This study was initiated to determine whether Karenitecin could potentiate radiosensitivity in T98G and MO59K glioma cell lines. Using clinically relevant doses of each agent, it was demonstrated that Karenitecin pretreatment significantly enhances radiosensitivity and was shown to be synergistic by isobolographic analysis. Karenitecin treatment resulted in a transient arrest in the G2/M phase of the cell cycle with an associated increase in expression of cyclin B1. It was further demonstrated that Karenitecin treatment results in activation of caspases, generation of reactive oxygen species, collapse of the mitochondrial membrane potential and inhibition of total protein kinase C, all of which could enhance radiosensitivity. These in vitro data suggest that Karenitecin has potential as a radiosensitizer in the treatment of malignant glioma.
DOI: 10.29245/2572.942X/2017/2.1109 View / Download PdfJoel Ramireza-b, Melissa F. Holmesa, Fuqiang Gaoa-b, and Sandra E. Blacka-c
With dementia prevalence on the rise, it is imperative to develop novel therapies and treatments to address the increasing recognition of the clinical and pathological overlap of Alzheimer’s and cerebrovascular disease - the top two leading causes of dementia. Although the research methods currently employed have made great advances towards our understanding of comorbid neurovascular and neurodegenerative diseases, these knowledge-based silos have had a tendency to operate in relative isolation. As our cumulative body of knowledge within each platform increases, so should the coordination of research. By examining current findings in neuroimaging, neuropsychology, genetics, neuropathology, and molecular neurobiology, this blanket-level mini-review will examine the spectrum of research findings that contributes to our understanding of Alzheimer’s and vascular contributions to dementia.
DOI: 10.29245/2572.942X/2017/1.1105 View / Download Pdf